Cholesterol efflux and uses thereof

Details Cholesterol efflux and uses thereof Cholesterol efflux and uses thereof

A - Human Necessities

61

K

A61K 31/713 (2006.01) A61K 31/7064 (2006.01) A61K 38/17 (2006.01) A61K 38/44 (2006.01) A61K 45/06 (2006.01) A61P 3/06 (2006.01) C12N 5/10 (2006.01) C12N 5/16 (2006.01) C12N 5/22 (2006.01) A61K 48/00 (2006.01)

Patent

CA 2500210

In a first aspect of the present invention, there is provided a method of modulating cholesterol efflux in a cell, said method comprising modulating expression and/or activity of sterol 27-hydroxylase (CYP27) and/or caveolin-1 in the cell. Applicants have found that cholesterol can be removed by cholesterol efflux which is regulated by CYP27 and/or caveolin-1. More suprisingly for CYP27 modulation the cholesterol effluxed remains in the form of cholesterol and not as oxidized cholesterol as would be expected in the presence of CYP27. Preferably, CYP27 is modulated in macrophages and caveolin- 1 is modulated in hepatic cells.

Selon un premier aspect, l'invention concerne un procédé de modulation du flux sortant de cholestérol dans une cellule. Ce procédé consiste à moduler l'expression et/ou l'activité du stérol-27-hydroxylase (CYP27) et/ou de la cavéoline-1 dans la cellule. Les déposants ont observé que le cholestérol peut être retiré par le flux sortant de cholestérol qui est régulé par CYP27 et/ou la cavéoline-1. Encore plus surprenant pour la modulation de CYP27, le cholestérol sortant demeure sous la forme de cholestérol et non pas sous forme de cholestérol oxydé comme ce que la présence de CYP27 pourrait laisser supposer. De préférence, CYP27 est modulé en macrophages et la cavéoline-1 est modulée dans les cellules hépatiques.

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